Nimodipine inhibits calcium-independent nitric oxide synthase activity in transient focal cerebral ischemia rats and cultured mouse astroglial cells.

Abstract:

:The effect of nimodipine on nitric oxide synthase (NOS) activities in brains in transient focal cerebral ischemia rats, in cultured mouse neurons and astroglial cells and bovine brain capillary endothelial cells (BCECs) was investigated. The administration of nimodipine (3 mg.kg(-1), p.o., twice a day, for 3 days) before middle cerebral artery (MCA) occlusion significantly reduced infarct size, decreased nitrite/nitrate (NOx) content and inhibited Ca2+-independent NOS activity in the infarct area. Nimodipine inhibited the Ca2+-independent NOS activity induced by lipopolysaccharide (LPS) + tumor necrosis factor alpha (TNF alpha) in mouse astroglial cells with an IC50 value of 0.036+/-0.003 mM and Ca2+-dependent NOS activity in mouse neurons with an IC50 value of 0.047+/-0.003 mM, but did not affect Ca2+-dependent NOS activity in BCECs. The inhibition of Ca2+-independent NOS activity by nimodipine in astroglial cells was competitive with respect to L-arginine. Nimodipine also inhibited the induction of Ca2+-independent NOS activity in vitro. These results suggest that nimodipine in addition to its cerebral vasodilating effect may protect brain from ischemic neuronal damage through modifying NOS activity.

journal_name

Life Sci

journal_title

Life sciences

authors

Zhu D,Li R,Liu G,Hua W

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

PL221-31

issue

15

eissn

0024-3205

issn

1879-0631

pii

S0024320599004099

journal_volume

65

pub_type

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